Titanium(IV) carboxylate complexes: Synthesis, structural characterization and cytotoxic activity

Four titanium(IV)carboxylate complexes [Ti(eta 5-C5H5)(2)(O(2)CCH(2)SMes)(2)] (1), [Ti(eta(5)-C5H4Me)(2)(O2CCH2SMeS)(2)] (2). [Ti(eta(5)-C5H5)(eta(5)-C5H4SiMe3)(O2CCH2SMeS)(2)] (3) and [Ti(eta(5)-C5Me5)(O(2)CCH(2)SMes)(3)] (4: Mes = 2,4,6-Me3C6H2) have been synthesised by the reaction of the corresponding titanium derivatives [Ti(eta(5)-C5H5)(2)Cl-2], [Ti(eta(5)-C5H4Me)(2)Cl-2], [Ti(eta(5)-C5H5)(eta(5)-C5H4SiMe3)Cl-2] and [Ti(eta(5)-C5Me5)Cl-3] and two (for 1-3) or three (for 4) equivalents of mesitylthioacetic acid. Complexes 1-4 have been characterized by spectroscopic methods and the molecular structure of the complexes 1, 2 and 4 have been determined by X-ray diffraction studies. The cytotoxic activity of 1-4 was tested against tumor cell lines human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells. that is peripheral blood mononuclear cells PBMC and compared with those of the reference complexes [Ti(eta(5)-C5H5)(2)Cl-2] (R1), [Ti(eta(5)-C5H4Me)(2)Cl-2] (R2), [Ti(eta(5)-C5H5) (eta(5)-C5H4SiMe3)Cl-2] (R3) and cisplatin. In all cases, the cytotoxic activity of the carboxylate derivatives was higher than that of their corresponding dichloride analogues, indicating a positive effect of the carboxylato ligand on the final anticancer activity. Complexes 1-4 are more active against K562 (IC50 values from 72.2 to 87.9 mu M) than against HeLa (IC50 values from 107.2 to 142.2 mu M) and Fem-x cells (IC50 values from 90.2 to 191.4 mu M). (C) 2009 Elsevier Ltd. All rights reserved.